(sef ix' eem).
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2-amino-4-thiazolyl)[(carboxymethoxy)imino]acetyl]amino]-3-ethenyl-8-oxo-, trihydrate, [6R-[6,7(Z)]]-.
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)glyoxylamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 72-(Z)-[O-(carboxymethyl)oxime]trihydrate [79350-37-1].
» Cefixime contains the equivalent of not less than 950 µg and not more than 1030 µg of Cefixime (C16H15N5O7S2) per mg, calculated on the anhydrous basis.
Packaging and storage Preserve in tight containers.
Labeling Label to indicate that it is the trihydrate form. Where the quantity of Cefixime is indicated in the labeling of any preparation containing Cefixime, this shall be understood to be in terms of anhydrous cefixime (C16H15N5O7S2).
USP Reference standards 11
Identification, Infrared Absorption 197K Prepare the test specimen as follows. Dissolve about 5 mg of it by trituration in 2 mL of methanol and evaporate with the aid of gentle heat to dryness.
Specific rotation 781S: between 75 and 88.
Test solution: 10 mg per mL, in sodium bicarbonate solution (2 in 100).
Crystallinity 695: meets the requirements.
pH 791: between 2.6 and 4.1, in a solution containing the equivalent of 0.7 mg of cefixime per mL.
Water, Method I 921: between 9.0% and 12.0%.
Tetrabutylammonium hydroxide solution, Mobile phase, Monobasic potassium phosphate solution, pH 7.0 Phosphate Buffer, Resolution solution, and Chromatographic system Proceed as directed in the Assay.
Standard solution Use the Standard preparation prepared as directed in the Assay.
Test solution Use the Assay preparation.
Procedure Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak areas. Calculate the percentage of each impurity in the portion of Cefixime taken by the formula:
0.1P(ri / rS)in which P is the potency, in µg per mg, of cefixime calculated in the Assay; ri is the peak area for each impurity; and rS is the cefixime peak area: not more than 1.0% of any individual impurity is found; and not more than 2.0% of total impurities is found.
Tetrabutylammonium hydroxide solution Dilute 25 mL of 0.4 M tetrabutylammonium hydroxide solution with water to obtain 1000 mL of solution, and adjust with 1.5 M phosphoric acid to a pH of 6.5.
Mobile phase Prepare a suitable filtered and degassed mixture of Tetrabutylammonium hydroxide solution and acetonitrile (3:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
Monobasic potassium phosphate solution Dissolve 6.8 g of monobasic potassium phosphate in water to make 500 mL of solution.
pH 7.0 Phosphate Buffer Dissolve 7.1 g of anhydrous dibasic sodium phosphate in water to make 500 mL of solution. Adjust a volume of this solution with a sufficient volume of Monobasic potassium phosphate solution to a pH of 7.0.
Resolution solution Dissolve USP Cefixime RS in water to obtain a solution having a concentration of about 1 mg per mL. Heat this solution at 95 in an oil bath for 45 minutes, cool, and use promptly.
Standard preparation Dissolve an accurately weighed quantity of USP Cefixime RS in pH 7.0 Phosphate buffer to obtain a solution having a known concentration of about 0.2 mg of cefixime (C16H15N5O7S2) per mL. Use this solution promptly.
Assay preparation Transfer about 110 mg of Cefixime, accurately weighed, to a 100-mL volumetric flask, dilute with pH 7.0 Phosphate buffer to volume, and mix. Transfer 10.0 mL of this solution to a 50-mL volumetric flask, dilute with pH 7.0 Phosphate buffer to volume, and mix. Use this solution promptly.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 12.5-cm column containing 4-µm packing L1. The flow rate is adjusted so that the retention time of cefixime is about 10 minutes. The column is maintained at a constant temperature of about 40. Chromatograph the Resolution solution, and record the peak areas as directed for Procedure: the relative retention times are about 0.9 for cefixime (E)-isomer and 1.0 for cefixime; and the resolution, R, between cefixime and cefixime (E)-isomer is not less than 2.0. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the column efficiency is not less than 4000 theoretical plates when calculated by the formula:
5.545(t / Wh/2)2the tailing factor for the analyte peak is not less than 0.9 and not more than 2.0, when calculated by the formula:
W0.1 / 2fin which W0.1 is width of peak of 10% height; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in µg, of cefixime (C16H15N5O7S2) in each mg of Cefixime taken by the formula:
500,000(C / W)(rU / rS)in which C is the concentration, in mg per mL, of cefixime in the Standard preparation; W is the quantity, in mg, of Cefixime taken to prepare the Assay preparation; and rU and rS are the cefixime peak areas obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2547Pharmacopeial Forum: Volume No. 29(3) Page 616